The electroretinogram, ERG, is a valuable noninvasive measure of retinal activity. It is commonly used for diagnosing and following the course of retinal diseases. By building upon discoveries by the retinal physiologist, the usefulness of the ERG, the summed activity of the retinal cells, can now be extended. During the current grant period we have provided strong evidence that the leading edge of the human rod ERG is quantitatively described by a recent model of rod phototransduction. This portion of the ERG is the sum of the activity of individual rod receptors. These findings indicate that the a-wave can be employed to answer fundamental questions about the transduction process of normal and abnormal human rods. These questions will be addressed by fitting models of transduction to ERGs from patients with a variety of retinal disorders. During the current grant period, we have also provide evidence that the human cone receptors can be studied in a similar way. One of the aims of the proposed research is to measure human cone receptor activity in vivo. and to develop techniques for testing hypotheses for disease related changes in cone function. This will be accomplished by fitting models of transduction to the cone isolated a-waves of normals, dichromats, and patients with different retinal diseases. Finally, by building upon the models of the receptor, models of the ERG that include the activity of the inner nuclear layer will be developed and applied to ERGs recorded from individuals with and without retinal problems.